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RegeneRx JV Presents Results of Phase 2b/3 (ARISE-1) Dry Eye Trial at ARVO 2017

Posted by australiandryeye on May 14, 2017 at 6:50 AM Comments comments (0)

ROCKVILLE, Md., May 9, 2017 /PRNewswire/ -- RegeneRx Biopharmaceuticals, Inc. (OTCQB: RGRX) ("the Company" or "RegeneRx"), a clinical-stage drug development company focused on tissue protection, repair and regeneration, announced that its joint venture, ReGenTree LLC, presented the results of its ARISE-1 Phase 2b/3 dry eye clinical trial in a poster session to physicians, scientists, and analysts today at the 2017 ARVO meeting in Baltimore, Maryland.


As previously reported, the double-masked, placebo-controlled trial in 317 patients with dry eye syndrome demonstrated that after 28 days of treatment, RGN-259 was safe and significantly reduced ocular discomfort both during and after exposure to a controlled adverse environment (CAE®;). Ocular discomfort is a symptom of dry eye syndrome. ReGenTree also reported that after 28 days of treatment RGN-259 significantly reduced total and inferior corneal fluorescein staining in a subgroup of subjects with compromised baseline tear film break-up time, which is a sign of dry eye syndrome. Both symptom and sign improvements are typically required by FDA to obtain marketing approval of a pharmaceutical treatment for dry eye.


A second Phase 3 dry eye trial (ARISE-2) designed to reproduce the results seen in ARISE-1 is currently underway in the U.S. with over 500 patients. The trial is expected to be completed by the fall of 2017.

 

About RGN-259 for the Treatment of Dry Eye Syndrome

 

RGN-259 is a sterile, preservative-free topical eye drop for ophthalmic indications whose active ingredient is Thymosin beta 4 (Tβ4). Based on U.S. Phase 2 and Phase 2b/3 clinical trials in moderate and severe dry eye syndrome, RGN-259 is safe and found to show statistically significant improvements in several signs and symptoms of dry eye, as well as positive trends in other outcome measures. The data from these trials, as well as a previously completed clinical trial of RGN-259 in patients with NK, reflect RGN-259's mechanisms of action, support the "protective" effects of RGN-259, and provide FDA-approvable clinical endpoints to be targeted in these and any future clinical trials. Dry eye syndrome is a multifactorial disease and it is well known that Tβ4 can elicit a spectrum of therapeutic responses, including promotion of cell migration and proliferation, reduction of inflammation and acceleration of corneal epithelial growth and would represent a major step forward from current treatment options.

 

About RegeneRx Biopharmaceuticals, Inc. (www.regenerx.com)

 

RegeneRx is focused on the development of novel therapeutic peptides, including Thymosin beta 4 (Tβ4) and its constituent fragments, for tissue and organ protection, repair and regeneration. RegeneRx currently has three drug candidates in clinical development for ophthalmic, cardiac and dermal indications, three active strategic licensing agreements in the U.S., China, and Pan Asia (Korea, Japan, and Australia, among others), and has patents and patent applications covering its products in many countries throughout the world. RGN-259, the Company's Tβ4-based ophthalmic drug candidate, has been designated an orphan drug in the U.S. for the treatment of neurotrophic keratopathy (NK). In March 2016, RegeneRx, through its U.S joint venture, ReGenTree LLC, completed a 317-patient Phase 2b/3 clinical trial in patients with dry eye syndrome. The dry eye trial results were announced in May 2016 and ReGenTree subsequently received permission from the U.S. FDA and has initiated a second Phase 3 trial in approximately 500 patients that is expected to be completed in the fourth quarter of 2017. ReGenTree is simultaneously conducting a 46-patient Phase 3 clinical trial in patients with NK. RGN-259 is also being developed in patients with dry eye syndrome in Asia through RegeneRx's two Asian partnerships. RGN-352, the Company's Tβ4-based injectable formulation, is a Phase 2-ready drug candidate designed to be administered systemically to prevent and repair cardiac damage resulting from heart attacks and central nervous system tissue damage associated disorders such as multiple sclerosis and traumatic injuries such as stroke. For additional information about RegeneRx please visit www.regenerx.com.

 

About ReGenTree LLC

 

ReGenTree is a U.S. joint venture company owned by GtreeBNT Co., Ltd, and RegeneRx Biopharmaceuticals, Inc. specifically to develop RGN-259 in the U.S. and Canada for ophthalmic indications. ReGenTree licensed the rights to RGN-259 from RegeneRx in 2015. While G-treeBNT is the majority owner of ReGenTree, RegeneRx retains a significant minority interest in the joint venture, in addition to a royalty on commercial sales, and is represented on the board of ReGenTree. Certain commercial and financial transactions require RegeneRx approval. G-treeBNT is responsible for operations of the venture and all funding required for clinical development of RGN-259 in the U.S. For additional information about ReGenTree, please visit www.regentreellc.com.

 

Forward-Looking Statements

 

Any statements in this press release that are not historical facts are forward-looking statements made under the provisions of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Forward-looking statements used in this press release relate to, among other things, the quality of clinical data, the activity of the active ingredient in our product candidates, and the expected timing of initiation and completion clinical trials in the United States and the potential benefits to RegeneRx of such trials. There can be no assurance that any proposed clinical trial will start within the estimated initiation timeframe or be completed within the estimated timeframe or that positive results from any clinical trials or research by the Company, its collaborators, or independent parties in the U.S. or any other country will result in subsequent clinical confirmation or future value. There can also be no assurance that any of the Company's drug candidates will result in any approved products in the U.S. or any other country. Please view these and other risks described in the Company's filings with the Securities and Exchange Commission ("SEC"), including those identified in the "Risk Factors" section of the annual report on Form 10-K for the year ended December 31, 2016, and subsequent quarterly reports filed on Form 10-Q, as well as other filings it makes with the SEC. Any forward-looking statements in this press release represent the Company's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. The Company specifically disclaims any obligation to update this information, as a result of future events or otherwise, except as required by applicable law.

 

SOURCE RegeneRx Biopharmaceuticals, Inc.

 

Related Links

 

http://www.regenerx.com


http://www.prnewswire.com/news-releases/regenerx-jv-presents-results-of-phase-2b3-arise-1-dry-eye-trial-at-arvo-2017-300454170.html

Shire pays $20M for Parions midstage dry eye drug

Posted by australiandryeye on May 13, 2017 at 3:35 AM Comments comments (0)

Shire will pay $20 million upfront, with a potential $535 million biobucks if all goes according to plan, for Parion Sciences’ dry eye candidate P-321 as it looks to boost its ophthalmology pipeline.


The deal sees Shire gain exclusive worldwide rights to develop and commercialize P-321, where it will also lead development. The biopharma added that Parion will have “an opportunity to co-fund” work on the medication.

 

P-321 works as an epithelial sodium channel (ENaC) inhibitor and is in phase 2, targeting tear volume deficiency and promoting ocular surface healing. ENaC is believed to block the absorption of tears, and help keep the ocular surface hydrated; current meds target the effects of ocular inflammation, so Parion thinks it has a different med on its hands than those on the market.

 

“Ophthalmics is a continued focus for Shire, and the program for P-321 will benefit from our development and commercial infrastructure and expertise,” said Shire CEO Flemming Ornskov, M.D., M.P.H.

 

“This is an opportunity to apply our knowledge and experience from ophthalmics and dry eye disease for further innovation in this space. If approved, P-321 would expand our eye care portfolio.”

 

“Advancing P-321 with Shire, an emerging global leader in ophthalmics, offers the expertise and resources to move this promising potential therapy for dry eye sufferers forward," added Paul Boucher, president and chief executive of Parion.

 

“This collaborative license agreement enables us the opportunity to contribute and participate in P-321’s success, while continuing our drive to progress Parion’s pipeline of novel therapies.”

 

Full financial details were not on show, but Shire will stump up $20 million in the form of a license payment, with an additional $20 million payment in the works if things go well in the shorter term. Longer term, Parion could see the deal worth up to $535 million in biobucks if it ticks all of the milestone boxes.

 

The biotech also has the option to co-fund through additional stages of development in exchange for boosted royalties. It can also choose to co-fund any sales push and “participate in the financial outcome from those activities,” according to the pact.


http://www.fiercebiotech.com/biotech/shire-pays-20m-for-midstage-for-parion-s-dry-eye-drug

Novaliq to study novel dry eye treatment

Posted by australiandryeye on May 13, 2017 at 3:35 AM Comments comments (0)

Novaliq announced plans to develop a treatment for ocular neuropathic pain and inflammation in individuals with dry eye disease.


The treatment is being developed in collaboration with the University of Cologne, Germany, the company announced in a press release. 

Dry eye disease (DED) with neuropathic ocular pain is frequently underserved, according to Novaliq. Molecules attempting to target the cannabinoid receptor system are often unstable in water-based formulations, but Novaliq’s EyeSol drug delivery system, which takes poorly soluble drugs and turns them into effective therapies, may help with the bioavailability, stability and efficacy of the cannabinoid-receptor targeting agents, the company said.


“Increasing evidence is available on the importance of neuropathic ocular pain in DED. Based on solid results of our ongoing test series we expect a significant impact of Novaliq’s first-in class Nov-07 program in comparison with existing DED drugs on an established DED mouse model,” Philipp Steven, MD, of the Ocular Surface Group at the department of ophthalmology, University of Cologne, Germany, said in the release. 

“We are now translating evidence from our experimental model into final, conformational studies in close cooperation with Novaliq for a phase 1 clinical study in the near future. Based on the preclinical results, we believe that the Nov-07 program will facilitate the treatment of [dry eye disease] utilizing a dual mode of action toward inflammation and ocular neuropathic pain.”


http://www.healio.com/optometry/business-of-optometry/news/online/%7B8d03abb1-75cc-4f68-b3de-fa9f6f4d60ca%7D/novaliq-to-study-novel-dry-eye-treatment

New View of Dry Eye Stresses Mechanisms Over Manifestations

Posted by australiandryeye on May 13, 2017 at 3:35 AM Comments comments (0)

The Tear Film & Ocular Surface Society (TFOS) presented the conclusions and recommendations of the TFOS Dry Eye Workshop II (DEWS II) during a special session of the Association for Research in Vision and Ophthalmology (ARVO) 2017 Annual Meeting in Baltimore, Maryland, yesterday.

TFOS is a nonprofit, global organization that aims to improve understanding of the composition and regulation of the preocular tear film and its function in maintaining the cornea and conjunctiva, preventing infection, and preserving visual acuity. The group is a collaboration among scientists, clinicians, and industry professionals.

Definition Updated


The first dry eye workshop, held in 2007, "launched an increase in basic and clinical research to better understand dry eye, which affects 40 million people in the [United States], 10 million severely," David A. Sullivan, PhD, senior scientist at the Schepens Eye Research Institute/Massachusetts Eye and Ear and associate professor at Harvard Medical School, Boston, told Medscape Medical News.

The DEWS II report, which will be published in late June in Ocular Surface Journal, presents "a global consensus of the epidemiology, mechanisms, diagnosis, management, impact, and classification" of the condition, Dr Sullivan said. "We're distributing the report to hundreds of thousands of eye care practitioners in many languages," he added.

Among the key points in the new report is an updated definition of dry eye that is more mechanistic. Whereas the 2007 definition emphasized the symptoms of the disease, the 2017 definition describes the underlying causes of the disease: "Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles," Jennifer P. Craig, PhD, MCOptom, the workshop vice-chair, said in a TFOS news release.

A Shifting View

Fifteen to 20 years ago, dry eyes were attributed, logically, to insufficient water. Since then, "we've learned a tremendous amount. Now we know that androgens affect the lid and the main lacrimal glands, and regulate the Meibomian glands," Dr Sullivan said.


In Sjogren's syndrome and complete androgen insensitivity syndrome, the Meibomian glands do not make enough oil to prevent evaporation of tears, triggering a cascade of events that ultimately damages the ocular surface. "The tears do not start to concentrate, and receptors on the cornea trigger sensations of pain and discomfort. This decreases the ability of the eye surface to hold water and increases the instability of epithelial cells, which may die," Dr Sullivan continued. Meanwhile, cytokines pour out and trigger inflammation.

The new description of the disease grew out of the realization that markers of dry eye reflect "a significant role for osmolarity and inflammation," said chair of the session J. Daniel Nelson, MD, associate medical director for specialty care for HealthPartners Medical Group and Clinics in St Paul, Minnesota. Since the first report, the technical literature related to dry eye has almost doubled, he added.

"Classically, we'd say that dry eye is aqueous or evaporative. We know now that most people have a combination," Dr Nelson said.

The new definition also recognizes a role for the neurophysiology in the sensory aspect of the disease, which emerged from the disconnect between signs and symptoms in some patients. An individual with signs, but not symptoms, may have a pre-dry eye situation, Dr Nelson suggested. The reverse — patients with symptoms but no signs — may actually have neuropathic pain and not dry eye.

Underlying Causes


The new report also delves into causes of dry eye, which include autoimmune diseases, eye surgery that damages the ocular surface, use of certain types of drugs (diuretics, beta-blockers, and topical medications for glaucoma), blepharitis, eyelids that turn in or out, overuse of contact lenses, and prolonged staring at a lit screen, which reduces blinking.

At the DEWS II session, researchers also discussed the design of clinical trials to assess new drugs. "Dry eye doesn't have a cure, and there isn't a treatment for Meibomian gland dysfunction, which is the major cause," Dr Sullivan said, adding that drugs approved by the US Food and Drug Administration are anti-inflammatories. "They deal with the situation downstream, but not the underlying problem."

Meanwhile, Dr Nelson shared with Medscape Medical News that he helps patients take "a Sherlock Holmes approach" to identifying actionable environmental triggers such as seasonal allergies, exposure to irritants at work, and cosmetics, creams, and cats. "A woman may go to bed with facial cream on, but anything touching the lower lid gets into the tear ducts very quickly," he said. Cat saliva on human bedding deposits allergens that can trigger dry eye even after the cat has relocated.

Some patients simply learn to live with dry eyes, perhaps by minimizing environmental triggers, Dr Nelson noted.

Paradoxically, dry eye is the leading cause of visits to eye care practitioners, yet one study estimates that slightly more than half of affected individuals have not sought professional care, Dr Sullivan said. He adds that "the prevalence has not been fully appreciated."

More than 150 clinicians and researchers worked on the 2017 report. "It's great bringing people from all over the world together to move our understanding forward and have increased research translate into new strategies to improve the quality of life for people with this common disease," Dr Sullivan added.

Numerous companies fund TFOS, including Alcon, Novartis, Shire, Allergan, Bausch + Lomb, Akorn, CooperVision, Dompé, Horus Pharma, Lubris BioPharma, Oculeve, Sun Pharma, TearLab, SIFI, Johnson & Johnson Vision Care, Carl Zeiss Meditec/ZEISS Group, Quint Health, Scope Ophthalmics, and Senju. The authors have disclosed no other relevant financial relationships.

TFOS DEWS II Report. May 7, 2017.


http://www.medscape.com/viewarticle/879675

Sylentis announces new preclinical and clinical data for its SYL1001 molecule during ARVO 2017

Posted by australiandryeye on May 10, 2017 at 1:30 AM Comments comments (0)

SYL1001 is a compound under investigation for the treatment of dry eye disease.


It is a product based on the novel technology RNA interference (RNAi), developed for the treatment of signs and symptoms of this illness.

 

At the Annual Congress of the Association for Research in Vision and Ophthalmology 2017, around 11,000 attendees will meet form the 7-11 of May in Baltimore, USA.

 

Madrid, May, 9th, 2017. In the framework of the Annual Congress of the Association for Research in Vision and Ophthalmology 2017 (ARVO), being held from the 7-11 of May in Baltimore (USA), Sylentis, a pharmaceutical company from the PharmaMar Group (MSE:PHM), presents new preclinical and clinical developments with its molecule SYL1001 for the treatment of dry eye disease. This is a product based on the novel technology RNA interference (RNAi), developed for the treatment of the signs and symptoms of this pathology.

 

This Congress will bring together more than 11,000 top eye and vision researchers and clinicians from around the world to explore cutting-edge basic and clinical science. “We are proud to be able to present our results to such a well prepared audience. We trust our technology, innovative in its field, and we hope that SYL1001 will soon be a real alternative for treating millions of people that suffer from dry eye disease around the world”, states Ana Isabel Jiménez, R&D Director of Sylentis.

 

Accordingly, Sylentis participates at this event with the presentation of data from various clinical and preclinical trials. On one hand, the stability results of SYL1001 in different commercial containers. The stability of the compound in various containers and conditions through time concludes that all the formats analyzed guarantee the integrity and specifications of the product.

 

On the other hand, Sylentis has presented the results of the study of this product in animal models, to evaluate its efficacy in the treatment of the symptoms and signs of dry eye disease. These patients have a deficit of mucine, a protein found in tears, a low density in the goblet cells and inflammation of the ocular surface. These studies have concluded that SYL1001, apart from reducing the feeling of ocular discomfort, it also improves the quality of the tear and reduces inflammation. In animal models, the statistical increase in the levels of mucine (MUC5A+) present on the eye´s surface has also been demonstrated, allowing for the formation of a tear film. In this same study, an increase in the density of goblet cell (those producing and secreting mucine) and also in tear secretion was observed. The inflammatory mediators of the eye surface also decreased after treatment.

 

Finally, the Company presents a third study that demonstrates the existing correlation between the preclinical and clinical results in the search for the optimum and most efficient dose. Both, in animal and human models, the concentration of 1.125% of SYL1001 was observed to be the most efficient, along with a very low incidence of adverse events.

 

Principle studies of Sylentis to be presented at ARVO 2017:

 

Stability study of SYL1001 eye drops (a siRNA compound) for DED in different containers (Posterboard Number: 476 – A0401)

Session: 7th of May of 2017, from 13:30 to 15:15 hours. Lead author: Verónica Ruz, et al. Regulatory Affairs, Sylentis, Spain.

 

Efficacy of SYL1001 in different animal models of Dry Eye Disease (Posterboard number: 458 – A0383)

Session: 7th of May of 2017, from 13:30 to 15:15 hours. Lead author: Ana Isabel Jiménez et al. R&D, Sylentis, Spain.

 

Clinical and preclinical study correlation for SYL1001, a new treatment for dry eye disease (Posterboard number: 2670 – A0260)

Session: 9th of May of 2017, from 8:30 to 10:15 hours. Lead author: María Victoria González et al. Clinical Department, Sylentis, Spain.

 

About SYL1001

SYL1001 is a drug based on RNAi that is administered as preservative-free eye drops; it selectively inhibits production of the TRPV1 receptor. These receptors are ion channels that mediate the transmission of ocular pain. SYL1001 is a small synthetic double-stranded RNA oligonucleotide (siRNA) with a novel and highly selective mechanism of action. Non-clinical studies conducted by Sylentis with SYL1001 have demonstrated it has high ability to inhibit this specific target and block the perception of ocular pain in animals .

SYL1001 is a product undergoing development for the treatment or prevention of ocular pain related to with dry eye syndrome, and has potential to be developed for other pathologies that cause ocular pain (corneal lesions, refractive surgery, etc.).

 

About RNA interference (RNAi)

RNA interference (RNAi) is a natural cellular process that regulates the expression of certain genes, providing a role in innate defense and development in animal and plants. This process is used to specifically silence genetic transcripts that encode protein-causing diseases. The therapeutic application of targeted siRNAs is booming given the specificity of gene silencing for a particular protein in a given tissue and the lack of side effects. This new approach to drug discovery is a promising technology that is rapidly moving in the translational research space.

 

About dry eye syndrome

Dry eye syndrome is a multifactorial disease of the tear film and ocular surface that produces symptoms of ocular discomfort, eyesight disorders, and tear film instability with potential damage to the ocular surface. Dry eye syndrome is accompanied by such symptoms as ocular pain, itching, stinging, and irritation of the eye tissues. It is a characteristic disease of developed countries, associated with pollution, air conditioning, the use of contact lenses, refractive surgery and continued use of computers. Moreover, the amount and quality of tears decrease with age. Prevalence is between 5% and 30% among people aged 50 or over, and it is more frequent in women.

 

Dry eye can be treated with cyclosporin drops or autologous serum, but there is as yet no specific product for chronic treatment of the ocular pain related to dry eye syndrome; oral analgaesics or anaesthetics are used in general. However, the main treatment consists of artificial tears, in the form of drops, gel or creams. Preservative-free eye drops have generally been found to offer the best long-term response.

 

About Sylentis

Sylentis, a company of PharmaMar (MSE:PHM), is a biotechnology company fully owned that develops innovative therapies harnessing the technology of post-transcriptional gene silencing or RNA interference (RNAi). Sylentis has developed an approach to efficiently design RNAi-based therapeutics that can be used to silence numerous disease-causing genes. We currently have a robust therapeutic program in ophthalmology with two candidates under development in Phase II studies for glaucoma (bamosiran) and ocular pain (SYL1001)II,III,IV. Sylentis is also developing new products for the treatment of several eye diseases such as ocular allergies and retina diseases. To know more about us, please visit us at www.sylentis.com.

 

Disclaimer

This document is a press release, not a prospectus. This document does not constitute or form part of an offering or invitation to sell or a solicitation to purchase, offer or subscribe shares of the company. Moreover, no reliance should be placed upon this document for any investment decision or contract and it does not constitute a recommendation of any type with regard to the shares of the company.


http://www.sylentis.com/index.php/en/news/professional-news/119-sylentis-announces-new-preclinical-and-clinical-data-for-its-syl1001-molecule-during-arvo-2017

Physicists working to cure 'dry eye' disease

Posted by australiandryeye on May 2, 2017 at 11:20 PM Comments comments (0)

The eye is an exquisitely sensitive system with many aspects that remain somewhat of a mystery—both in the laboratory and in the clinic. A U.S.-based team of mathematicians and optometrists is working to change this by gaining a better understanding of the inner workings of tear film distribution over the eye's surface. This, in turn, may lead to better treatments or a cure for the tear film disease known as "dry eye." They describe their work in the journal Physics of Fluids.

Dry eye disease afflicts millions of people worldwide, with symptoms such as pain, dryness, redness, reduced visual acuity, and feelings of grittiness. While drops can provide some temporary relief, dry eye conditions can damage the cornea and, over time, result in reduced visual function.

When the tear film functions properly, a thin liquid film coats the eye surface during a blink by the upper eyelid, creating a smooth optical surface for vision and allowing us to see clearly.

"With dry eye, this optical function is disrupted by either insufficient tear volume or by excessively rapid evaporation of water from the tear film," explains Richard Braun, a professor in the University of Delaware's Department of Mathematical Sciences. "In either case, the tear film may not be able to form a smooth optical interface for a sufficiently long time to allow normal eye function."

The tear film on the surface of the eye is a very thin fluid layer—only a few millionths of a meter thick. This thickness is less than 1,000 times the size of the eye opening, which is approximately 1 centimeter.

Braun and colleagues "took advantage of this difference in sizes to develop simplified mathematical models that work quite well to capture experimentally observed phenomena in vivo," he said.

Once the team created a mathematical model, they were able to solve it using numerical methods in the computer appropriate for solving the equations on irregularly shaped domains like the shape of the exposed area of the eye. "We use and extend a computational framework called 'Overture,' which was originally developed at Lawrence Livermore National Laboratory," Braun added.

Under the assumptions of their model, the team quantified the dynamics all over the exposed ocular surface, and the results agreed well with in vivo observations of the tear film gained from fluorescence imaging. "Our mathematical results captured how tear fluid makes its way around the eyelids to the drainage holes called 'puncta,' in the inside corner of the eye," he said.

Among the team's key findings was verifying that it takes "a blink" to redistribute tear film. "The evaporated tear film on the front of the eye can't be replenished by simply supplying more new tear fluid from the lacrimal gland," Braun noted.

Braun believes their results "may aid in the development of better treatments for dry eye, and also add valuable context and understanding for current imaging techniques used to observe tear film dynamics."

Explore further: Mathematicians model heat flow in human tears

More information: The article, "Tear Film Dynamics with Evaporation, Wetting, and Time-Dependent Flux Boundary Condition on an Eye-Shaped Domain" is authored by Longfei Li, Richard J. Braun, Kara L. Maki, William Henshaw, and P.E. King-Smith. It will be published in the journal Physics of Fluids on May 6, 2014. DOI: 10.1063/1.4871714

Read more at: https://phys.org/news/2014-05-physicists-eye-disease.html#jCp

Allergan receives FDA approval for electrical dry-eye device

Posted by australiandryeye on May 2, 2017 at 11:15 PM Comments comments (0)

 


Allergan has gotten Food and Drug Administration approval to market its TrueTear Intranasal Tear Neurostimular, a device the company says increases tear production using electrical stimulation.


Allergan, with headquarters in Dublin and New Jersey, has a unit in Irvine, where it was previously based until it was acquired for about $70 billion by Dublin-based Actavis Plc.


TrueTear, Allergan said in a statement, is the first FDA-approved device to increase tear production in adult patients using neurostimulation. The handheld stimulator includes disposable tips that are placed in the nasal cavity, which induces tear production.


“TrueTear represents a technological breakthrough for eye care professionals as it delivers an effective, non-invasive and drug-free way to temporarily increase tear production,” David Nicholson, chief research and development officer, at Allergan, said in a statement. “As an innovator in eye care, we are continually looking for new products to offer through our portfolio, and TrueTear represents the next step forward.”


Allergan has long been rooted in the eye care industry. In the early 1950s, it developed eye drops to treat allergies and acts as decongestants.

http://www.ocregister.com/2017/05/01/allergan-receives-fda-approval-for-electrical-dry-eye-device/

Could a tear cure dry eyes?

Posted by australiandryeye on May 2, 2017 at 11:15 PM Comments comments (0)

British scientists have patented the design of a biological tear that could be used by millions of people who suffer with eye problems caused by their own tears not working properly.

The most common treatments for dry eyes are lubricants, ointments or artificial tear fluids made from polymers such as methlycellulose (a component of wallpaper paste).

But researchers at Oxford University have discovered the secret of the essential ingredients of real tears, and are working towards developing drops based on the proteins and fats in the real thing.

Most people associate tears with crying, but they play a vital role in the visual system every minute of the day. As well as being a super-efficient cleaning fluid, they sluice foreign objects from the eye, get rid of noxious fumes such as those given off by onions, and provide biological protection from infections.

They also keep the eye clean and moist - working like car windscreen wash-ers every time we blink - and feed the cells of the cornea. Because the cornea has no blood supply, the tears carry oxygen and essential nutrients to the tissue cells and take the waste products away.

A lack of tears can often result from effects of some medications such as anti-histamines, oral contraceptives and antidepressants. Tear production also naturally decreases with age, resulting in dry eyes, which can feel hot and gritty and appear red and swollen.

'Every time we blink, we spread a thin layer of tear over the eye,' says Dr John Tiffany, lecturer and tear researcher at Oxford University. 'Normally the eye blinks pretty rapidly to constantly refresh the tear layer, but when, for example, people stare at a computer screen for a long time, the layer breaks up and that can result in damage.

'Problems such as the air pollution from the general urban environment or as a result of specific working conditions are increasing, and mean that in some cases people have to use eye baths to get rid of the irritation.'

He says eye drops and other products use a variety of artificial polymers but, as yet, there is no completely satisfactory formula for tears.

The researchers are planning talks with pharmaceutical companies about the future development of the Oxford tear. 

Read more: http://www.dailymail.co.uk/health/article-7676/Could-tear-cure-dry-eyes.html#ixzz4fyx8F04Y

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Not all MGD is dry eye

Posted by australiandryeye on May 2, 2017 at 11:15 PM Comments comments (0)

"The prevalence of asymptomatic MGD is likely higher than we all realize. If we can find MGD and treat the anatomy early, we can save functioning glands and put the patient in a better position to have a healthier tear film long term. Regrettably, a recent survey of practitioners showed that only 30% routinely screen for MGD. Furthermore, work from our own group at Duke is showing that a large percentage of patients coming in for preoperative evaluation have underlying dry eye and MGD.


Screening is now the practice of the leading few, not the majority. I can only hope we recognize as a whole that screening is critical."


Read more at: http://www.healio.com/ophthalmology/cornea-external-disease/news/blogs/%7B01048fb5-5472-4197-95b6-b7249dd67190%7D/preeya-k-gupta-md/blog-not-all-mgd-is-dry-eye

Nicox first quarter 2017 business update and cash position

Posted by australiandryeye on May 2, 2017 at 11:05 PM Comments comments (0)


Resubmission to the U.S. FDA, by Nicox, on March 8, 2017 of the NDA for ZERVIATE (cetirizine ophthalmic solution) 0.24%, Nicox’s novel, proprietary, cetirizine eye drop formulation for the treatment of ocular itching associated with allergic conjunctivitis.


http://www.nicox.com/news-media/nicox-first-quarter-2017-business-update-cash-position/

Novartis to strengthen R&D pipeline by in-licensing ECF843 for ophthalmic indications

Posted by australiandryeye on April 9, 2017 at 9:00 AM Comments comments (0)

Novartis exercises an option to in-license ECF843, a recombinant form of human lubricin from Lubris LLC, for ophthalmic indications worldwide (outside Europe)

Dry eye is an area with high unmet medical need, impacting over 344 million patients globally[1]


ECF843 is a new therapeutic approach and potential first-in-class Rx treatment in dry-eye, which in a small phase II study[2] showed the potential to provide instant relief of symptoms and improve signs


This in-licensing will build upon Novartis' leadership in dry eye with global artificial tear products including Systane®, Tears Naturale® and Genteal®


Basel, April 6, 2017 - Novartis announced today that it has exercised an option to in-license ECF843 for ophthalmic indications worldwide (outside Europe). The closing of the deal is subject to customary closing conditions including regulatory approvals. The financial and other terms of this transaction are not disclosed.



ECF843 is a recombinant human lubricin (rh-Lubricin) protein, developed by Lubris LLC, Boston, USA. Instant relief of dry eye symptoms by improving signs in a timely manner remains a high unmet medical need and a relevant factor for patient compliance and treatment success. In a small phase II clinical study[2], ECF843 demonstrated the potential to provide immediate improvement of symptoms likely by increasing lubrication across various eye and tear surfaces together with an improvement in signs of dry eye within 28 days - without reporting treatment-related adverse events.



"ECF843 has the potential to be the first therapeutic to provide rapid relief of dry eye symptoms and significantly improve signs," said Vasant Narasimhan, Global Head, Drug Development and Chief Medical Officer, Novartis. "Exercising our option to in-license ECF843, along with our recent acquisition of Encore Medical for the treatment of presbyopia, underscores our commitment to treating diseases of the front of the eye which impact millions of people worldwide"



Lubricin protein deficiency is observed in dry eye patients. Lubricin is an endogenous glycoprotein expressed in areas of high shear stress and friction including the tear film where it binds to and protects tissues of the ocular surface, the assumed mechanism that ECF843 addresses. ECF843 is a new therapeutic approach and a potential first-in-class Rx treatment in dry-eye, which is an area of high unmet medical need impacting over 344 million patients globally.[1]ECF843 is hypothesized to restore the tear film function, reduce friction and relieve the signs and symptoms of dry eye.



This in-licensing builds upon Novartis' leadership in ophthalmology and dry eye treatments with a global portfolio of artificial tear products that includes Systane®, Tears Naturale® and Genteal®.



Disclaimer

The foregoing release contains forward-looking statements that can be identified by words such as "to strengthen," "pipeline," "potential," "builds," "portfolio," "subject to customary closing conditions," "expect," "commitment," "hope," will," "hypothesized," or similar terms, or by express or implied discussions regarding potential completion of the announced in-licensing of ECF843, or regarding potential marketing approvals for ECF843, or regarding potential future revenues from ECF843 and the other products in the Novartis dry eye portfolio. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the proposed in-licensing will be completed in the expected form or within the expected time frame or at all. Neither can there be any guarantee that ECF843 will be submitted or approved for sale in any market, or at any particular time. Nor can there be any guarantee that ECF843 or the other compounds in the Novartis dry eye portfolio will be commercially successful in the future. In particular, management's expectations regarding ECF843 and the other compounds in the Novartis dry eye portfolio could be affected by, among other things, regulatory actions or delays or government regulation generally, including a failure to obtain necessary government approvals for the in-licensing of ECF843, or delays in obtaining such approvals; the potential that any other closing conditions for in-licensing of ECF843 might not be met; the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; competition in general; global trends toward health care cost containment, including ongoing pricing and reimbursement pressures; safety, quality or manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.



About Novartis Ophthalmology


Novartis is a leading ophthalmology company, with therapies that treat both front and back of the eye conditions, including retina diseases, glaucoma, dry eye and other external eye diseases. In 2016, Novartis combined its retina medicines business with the Alcon pharmaceuticals business, now operating as one Ophthalmology franchise under Novartis Pharmaceuticals.


About Novartis


Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2016, the Group achieved net sales of USD 48.5 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.


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References


[1] Market Scope 2016 Dry Eye Products Report: A Global Market Analysis for 2015 to 2021.

[2] The Ocular Surface, Vol. 15, Issue 1, p. 77-87.


https://www.novartis.com/news/media-releases/novartis-strengthen-rd-pipeline-licensing-ecf843-ophthalmic-indications

Protein agent may change approach to treating dry eye, inflammation

Posted by australiandryeye on March 24, 2017 at 8:15 AM Comments comments (2)

Take-home: Recombinant human lubricin showed potential as a new therapeutic approach to the management of dry eye disease in a small clinical trial. Compared with sodium hyaluronate, lubricin (Lubris BioPharma), significantly improved both signs and symptoms of moderate dry eye after two weeks of treatment.

 

Patients with moderate dry eye disease experienced significant improvement in signs and symptoms following a two-week clinical trial of a recombinant version of the human protein lubricin (Lubris BioPharma) compared to sodium hyaluronate (HA).

 

Although lubricin is still an investigational agent, it shows promise as an innovative approach to preventing or reducing ocular inflammation, said Paul Karpecki, OD, an expert on ocular surface disease.

 

In this randomized, double-masked, parallel group safety and efficacy trial and 1-week follow-up, 19 patients were treated with lubricin 150 µL eye drops and 20 with HA 0.18% eye drops.

 

Subjects receiving lubricin experienced greater than 70% reduction in their symptoms from baseline. Improvements against HA were reported for foreign body sensation (p < 0.013), sticky feeling (p < 0.0432), blurred vision (p < 0.0013), and photophobia (p < 0.011) in at least one eye.

 

Improvements shown

 

Lubricin also demonstrated statistically significant improvements against HA in the following objective signs of dry eye: corneal fluorescein staining (OD/OS: 43.8%, 50.0%, vs. 26.5%, 23.3%, p < 0.0398, p < 0.0232), TFBUT (p < 0.010), eyelid erythema (p < 0.004), conjunctival erythema (p < 0.0013), and daily mean instillations (p < 0.04). No adverse effects related to lubricin were reported during the trial.

 

A key point from the trial was the statistical improvement in both signs and symptoms, Dr. Karpecki said, adding that the improvements in corneal staining, symptoms, and visual acuity amount to a “trifecta,” hinting at the potential of lubricin.

 

Results of the study were published in The Ocular Surface. The study was sponsored by Lubris BioPharma and Dompé Farmaceutici and was conducted at the Policlinico Umberto I, Sapienza University of Rome.

 

The molecule lubricin is one of the most lubricating and adhesive proteins in the body and is found on the ocular surface. It protects tissue surfaces from friction-related damage and wear, but its production may become impaired due to inflammation.

 

The hypothesis behind the development of recombinant lubricin is that by reducing friction it could interrupt the inflammatory cascade and help restore proper function in the treated area.

 

“This is exciting,” said Dr. Karpecki, who is in private practice in Lexington and Louisville, KY. He was not involved in the study. “The new area of interest is going to be proteins.”

 

Lubricin is one of a number of proteins found in tears and one of the most lubricious, making it an important barrier against ocular surface damage.

 

Commenting further on the trial findings, he noted that a small study with about 20 patients in each arm would not ordinarily be expected to produce statistically valid outcomes.

 

“The fact that it did really impress me,” Dr. Karpecki said. “It amazes me that you can get that kind of success with such a small N number, which bodes well for the future of this product.”

Blurred vision outcome

 

One finding that stood out was the day 14 outcome for blurred vision, Dr. Karpecki said, explaining that significant improvement often takes longer. In the left eye, lubricin supplementation achieved a 74.4% reduction from baseline compared to 56.3% in the HA group. However, it will be important to assess the efficacy of lubricin over longer periods in future studies.

 

The study design in which lubricin was compared with HA is also highly relevant, he said. HA is the most prescribed treatment for dry eye in most countries, although not in the United States.

 

“That in itself is fairly bold, to say we’re going to go up against number one and see if we can be equal,” he said. “In this case, they were far superior, and especially with a relatively small number of patients in each group.”

 

 

Paul Karpecki, OD

 

E: [email protected]

 

Dr. Karpecki is a consultant to Lubris BioPharma.


Novel topical peptide for dry eye tackles underlying cause of disease

Posted by australiandryeye on March 24, 2017 at 8:05 AM Comments comments (0)

 

A first-in-class topical synthetic peptide being developed as a treatment for dry eye disease (Lacripep, TearSolutions Inc.) is set to enter into clinical development.

 

The novel proprietary agent, planned to enter a phase I/II trial in March 2017, is a fragment of lacritin, a naturally occurring, eye-selective tear glycoprotein. The agent was discovered in 2001 by Gordon W. Laurie, PhD, professor of cell biology and ophthalmology, University of Virginia, Charlottesville, and chief scientific officer and cofounder, TearSolutions Inc., Charlottesville, VA.

 

“Lacritin is largely released into tears by acinar cells of the lacrimal gland, although it is also produced by other cells, including those of the meibomian gland,” Dr. Laurie said.

 

Findings from laboratory and preclinical research have included collaborators from James Madison University; Eastern Virginia University; Cornell Univesity; University of California, San Francisco; University of Southern California; and University of Western Ontario.

 

 

Tears stimulated

 

Their research has found that the treatment topically stimulates basal tear secretion and wound healing, helps restore ocular surface cells to normal, and is deficient in the tears of persons with various kinds of dry eye disease.

 

“[The agent] has the same properties as the parent molecule, and unlike all existing therapies for dry eye disease, appears to address an underlying cause of the disorder rather than a downstream consequence,” Dr. Laurie explained. “Analogous to insulin treatment for diabetes, [lacritin] essentially represents a replacement therapy to correct an existing deficiency. For that reason, we believe it holds exciting promise as a very safe and effective therapy.”

 

The development history of the agent dates back to 1991 when Dr. Laurie was searching for a research topic at the University of Virginia.

 

“I was struck by the fact that no one seemed to be addressing the biological basis of dry eye disease other than downstream inflammation,” he added.

 

Dr. Laurie approached the National Eye Institute with his ideas. He submitted and received funding to biochemically screen for natural regulators of tear secretion.

 

“Trying to identify this natural tear stimulatory activity was like looking for a needle in a haystack,” he said. “The needle was the novel protein that we named lacritin.”

 

The first lacritin experiments showed it was released by lacrimal acinar cells and promoted tear secretion. In addition, lacritin was found to be important for the health and homeostasis of the ocular surface epithelium as evidenced by its ability to rescue cultured corneal epithelial cells stressed by exposure to inflammatory cytokines.

 

No other tear protein appears to share these properties because the capacity of healthy control tears to rescue inflamed cells was lost when tears were depleted of lacritin,” Dr. Laurie outlined. “Furthermore, tears from persons with dry eye lack lacritin and failed to promote health, but gained this benefit when spiked with lacritin.”

 

Mechanistic studies revealed mitochondrial function was restored. Lacritin was also found to transiently stimulate autophagy, the physiological process that maintains homeostasis by removing damaged proteins and cell organelles which accumulate when cells are stressed, such as by inflammation.

 

“By restoring a more normal ocular surface condition, lacritin appears to remove triggers that give rise to inflammation, thereby breaking the vicious cycle that perpetuates inflammation in dry eye disease,” Dr. Laurie said.

 

Results of preclinical studies in animal models showed lacritin was effective in promoting tear secretion, restoring ocular surface integrity, and reducing focal infiltration of inflammatory CD4+ T cells in lacrimal glands.

 

“In the animal studies, we found these benefits were achieved quickly and were persistent,” Dr. Laurie said.

 

In order to translate lacritin’s benefits into clinical use, the focus turned to creating a synthetic lacritin peptide which is smaller, easy to manufacture, and retains all of lacritin’s known activities. The final therapeutic agent consists of the lacritin C-terminal fragment.

Phase I/II trial plans

 

The first in-human study aims to enroll 201 patients with Sjögren’s syndrome dry eye. Patients will be randomly assigned into 3 groups to receive 1 of 2 doses of the lacritin agent or placebo for 4 weeks at a frequency of 3 times per day.

 

The initial clinical trial is focusing on Sjögren’s syndrome because clinical features are better defined in Sjögren’s dry eye compared with other forms of dry eye, Dr. Laurie said. Therefore, variability that commonly plagues dry eye studies will be reduced.

 

“We expect [the agent to] have benefit across the full spectrum of the condition because lacritin deficiency is apparent in all forms of dry eye,” Dr. Laurie added.

He also noted that although the therapy is administered 3 times daily in the first clinical trial, findings from preclinical studies suggest that once-a-day dosing may be feasible.

 

“We found that [lacritin] remained stable in rabbit tear film for 24 hours,” Dr. Laurie said. “Thus, it may have long acting activity.”

 

Safety is not expected to be a concern because no dose-limiting toxicity was observed in animals, he added.

 

“That is not surprising considering [the agent], like lacritin, is naturally occurring in human tears,” Dr. Laurie said.

 

 

Gordon W. Laurie, PhD

 

E: [email protected]

 

Dr. Laurie is co-founder and chief scientific officer of TearSolutions Inc. He is also an inventor on a number of issued and pending lacritin patents licensed by TearSolutions.


http://ophthalmologytimes.modernmedicine.com/ophthalmologytimes/news/novel-topical-peptide-dry-eye-tackles-underlying-cause-disease

AXIM Biotech Retains Ora to Manage Upcoming Product Development and Clinical Trials on Glaucoma and Dry Eye Indications

Posted by australiandryeye on March 21, 2017 at 11:50 PM Comments comments (1)

NEW YORK, March 21, 2017 (GLOBE NEWSWIRE) -- AXIM® Biotechnologies, Inc. (AXIM® Biotech) (OTC:AXIM), a world leader in cannabinoid research and development, today announced that it has retained the services of Ora®, Inc., a global Contract Research Organization (“CRO”;), to perform the company’s upcoming product development (based on AXIM’s IP) and clinical trials for treating glaucoma and dry eye utilizing cannabinoid-based therapeutics. Ora is the world’s leading ophthalmology CRO for advancing products from pre-clinical through approval and post-market phases.


 

Ora will run the clinical programs under the supervision of Prof. Robert Ritch, Surgeon Director Emeritus and Chief of Glaucoma Services at New York Eye and Ear Infirmary of Mount Sinai School of Medicine in New York (NYEE). Prof. Ritch is a world-renowned expert in ophthalmology and glaucoma in particular, and has joined AXIM’s Advisory Board in December 2016.


 

“We are very pleased to team up with Ora, a world-class ophthalmology CRO, to guide our product development and clinical trials,” said George E. Anastassov, MD, DDS, MBA and Chief Executive Officer of AXIM Biotech. “Glaucoma and dry eye are highly prevalent ophthalmic diseases that require new and improved treatment options for patients. We look forward to working with Prof. Ritch and Ora in the development and clinically testing the efficacy of AXIM’s novel, proprietary, cannabinoid based solutions in treating glaucoma and dry eye and improving patients' well-being.”


 

“Despite new product approvals, glaucoma and dry eye remain ophthalmic diseases with significant unmet medical needs. Approximately 40% of glaucoma patients require more than one IOP-lowering medication. We hope that the development of new treatments with novel mechanisms of action will in turn reduce the risk of progression of visual field loss,” said David A. Hollander, MD, MBA, Chief Medical Officer of Ora. “Dry eye is one of the leading reasons for patient visits to eye care specialists. Novel therapies that address the signs and symptoms of dry eye disease will be welcomed by both dry eye sufferers and physicians.”


More info here: http://finance.yahoo.com/news/axim-biotech-retains-ora-manage-130000289.html

Lacritin Clinical Trials Begin mid-April

Posted by australiandryeye on March 18, 2017 at 9:10 PM Comments comments (0)




A University of Virginia Researcher has developed a formula that for the first time treats the causes, not just the symptoms, of dry eyes.


Millions of Americans suffer from dry eyes. To date, over-the counter drops don’t help much.


Gordon Laurie is a professor of cell biology at the University of Virginia and he says the prescription drugs treat only the inflammation, not the cause. He’s been working on this problem for 32 years, and says, he thinks he can fix it.


His drops go to clinical trials in March. If successful, Lacripep, the first drug to treat the cause of dry eyes, could be on the market in four years.


Listen to further audio with the Founder, Prof. Gordon Laurie here.


Clinical trial sites listed on TearSolutions: http://www.tearsolutions.com/Clinical_Trial_Sites.html


Looking at the Full Picture: Dr. Jennifer Rayner

Posted by australiandryeye on March 14, 2017 at 2:10 AM Comments comments (0)



Based in Adelaide, Australia, she is Co-owner with Dr. Rene Malingre and is the principal optometrist at Alleve Eye Clinic that, at this point, is the only known stand-alone clinic in Australia exclusively treating dry eye patients. She hopes that establishing Alleve as a stand-alone clinic ensures that other optometrists “don’t feel threatened” to refer their clients, knowing that Dr. Rayner will refer them back for non-dry eye needs. At this point, the clinic is dedicated to dry eye twice a week but her objective is to transition it to a full-time dedicated clinic.


 

And there is certainly the need for such a clinic.


Read the full article here.

UAB Optometry awarded grant for dry eye research

Posted by australiandryeye on March 7, 2017 at 6:50 PM Comments comments (0)

 

Written by Keaira Turner


Media contact: Alicia Rohan, [email protected]


University of Alabama at Birmingham School of Optometry researchers have been awarded a $1.9 million grant to study potential molecular markers in patients that could predict structural and functional changes of the eye in dry eye disease, and may lead to a targeted therapy.


“Dry eye is the most frequent eye disease that an eye care practitioner sees,” said Jason Nichols, O.D., Ph.D., professor in the UAB School of Optometry and assistant vice president for Industry Research Development in the UAB Office of the Vice President for Research and Economic Development. “The study will look at the lipid layer of the eye and the biochemical changes that cause dry eye. Once we understand these changes, we will be able to better treat the condition that affects up to 30 percent of the world.”


The National Eye Institute-funded study focuses on the impact of one of three layers on the eye, the outer lipid layer, an oil-based layer produced by glands that line the eye, sealing the tear film. The lipid layer helps decrease evaporation of our natural tears and provides a smooth surface needed for optimal vision. The lipid layer is where the problem lies for most people who develop dry eye symptoms.


 

Nichols was recently recognized as a top leader in the contact lens industry by Contact Lens Spectrum.


Nichols looks to target and identity the fatty acids that decrease the tear film, and their structural impact on the eye, using custom-built optical systems capable of measuring the very thin tear film. This study will help determine the functional impact of the lipid layer that increases the evaporation of the thinning tear film, causing dry eye.


 

“We hope to find the specific lipid that has been altered in the lipid layer to be able to provide patients with targeted treatment by either replacing the lipid or fixing the glands so they express the right amount of lipids,” Nichols said.

Boston's Dry Eye Pioneer Donald R. Korb OD

Posted by australiandryeye on March 7, 2017 at 3:50 AM Comments comments (0)

By David Bagdon, Publisher


Dry eyes are not a new phenomenon, in fact; most people have experienced them at various times throughout their lives. In most cases, dry eyes are a nuisance causing minor discomfort often brought about by eye strain or exposure to dry, windy conditions. However, for those suffering from chronic dry eye, the problem can cause significant pain and discomfort that can result in damage to the surface of the eye. It is estimated that over 25 million people in the United States and some 300 million worldwide suffer from dry eye.


Dr. Donald Korb of Korb and Associates, based in Boston, is widely recognized as one of the leading researchers and experts on the matter of chronic dry eye. Dr. Korb has been studying the issue for some 30 years and has published over 100 papers on the topic. As he explains, the issue first came to his attention in 1980 as he was researching and developing extended wear contact lenses.

To his surprise, several subjects in the study showed an unusual intolerance to this type of contact lens which led him to develop a hypothesis that the problem was tied to an oil deficiency on the surface of the eyes. While the accepted belief at that time was that dry eyes were the result of inadequate tear production, Dr. Korb was convinced that dry eye was due to an oil deficiency related to obstruction and dysfunction of the small Meibomian glands that line each eyelid.


When functioning correctly, the Meibomian glands serve to coat the ocular surface with oil to preserve moisture, while dysfunctional ones allow rapid evaporation and the resulting dryness. Dr. Korb teamed up with Dr. Antonio Henriquez of Barcelona, Spain, and the result was the discovery that the affected subjects in the study were suffering from obstructed Meibomian glands which resulted in the contact lens discomfort. Dr. Korb named the condition Meibomian gland dysfunction (MGD).


“What was difficult to believe is that a competent eye doctor could closely examine the eyes and the lids, yet would be unable to determine that the glands were obstructed without special tests utilizing pressure. In our original scientific article we stressed that the condition was not obvious. A thorough review of the non-obvious nature of Meibomian gland dysfunction was published in 2010. The difficulty in making this diagnosis led me to invent a device known as LipiView which is now used routinely to make this evaluation,” Dr. Korb said.


After identifying the problem, Dr. Korb directed his full focus to both research and the treatment of patients dealing with MGD. As he discovered, the Meibomian glands are small and delicate and if they are not producing quality oil, the problem can quickly deteriorate into acute inflammation. Due to his background as a researcher, Dr. Korb was able to rapidly study patient problems that arose in his own practice.


In order to diagnose and treat the problem of MGD on a much broader basis, he co-founded a company called TearScience which not only pioneered the LipiView tear evaluation device, but also produced LipiFlow, a device that simultaneously heats the inner lid surfaces while applying pulsatile pressure in order to improve oil flow and diminish inflammation. To date, the device is being used in over 250 eye care practices with over 100,000 patients having received treatment.


When asked about the significance of his invention, he looks back on that period as both challenging and rewarding.


“LipiFlow has been an exciting experience, perhaps the most exciting of my life. While I have over 20 inventions, 10 of which have been marketed, the complexity of developing the science of thermal pulsation treatment was by far the most complex. Although I have chosen not to be involved with the operation of the business, preferring research and clinical practice, seeing TearScience grow to employ over 100, including 10 engineers, has been like a dream,” he said.


“In addition, having had access to tens of millions of dollars for this research, we’ve had funding for many clinical studies and discoveries which are now in clinical practice to be used by all without fees,” he added. “This could not have been better or more exciting! I regularly receive letters from dry eye sufferers around the world who I have never met; that is a source of great gratification to me.”


Although Dr. Korb’s efforts have helped literally thousands of patients address their MGD and regain ocular comfort, he is concerned about the impact of electronic devices such as smart phones, tablets and computers on future generations. One issue that exacerbates MGD is extended screen time, not just from the standpoint of eye strain, but because it reduces one’s blink frequency, an action that is critical to the distribution of oil on the ocular surface.


According to Dr. Korb, our society’s dependence on electronic devices is likely to result in a dramatic increase in MGD over the coming years. In fact, he indicates he is already seeing an unusual increase in the number of cases involving young people and teens.


“Our group recently published a report in a prestigious journal titled ‘Dry eye is the wrong diagnosis for millions’. The correct diagnosis for over 80 percent of those suffering from dry eye is Meibomian gland dysfunction,” he said. “This is important for the future because the professions must recognize that obstruction of the glands is the usual cause of dry eye and that a key factor in this obstruction is inadequate blinking. It is well documented that excessive screen time dramatically reduces a person’s blink rate.


“In fact, a recent study conducted by our group showed that the incoming class at a prominent health care school already had concerning signs of dry eye. Based on the latter study, which will be published this year, 62 percent had symptoms which worsened as the day progressed, 41 percent were forced to use artificial tear supplements daily, 17 percent had discomfort using a computer, and over 50 percent had significant atrophy and permanent loss of at least 20 percent of their Meibomian glands. Dry eye is on its way to becoming a major public health problem and will only increase unless a government funded task force is enlisted to combat what is already a vocationally disabling disease for many.”


One of the most notable things about the way Dr. Korb addresses problems with dry eye is his very deliberate and methodical approach to diagnosis and treatment. Most likely a product of his background as a researcher, he methodically tests and reevaluates patients over a course of several appointments. In all cases he records copious notes about what is and isn’t improving. He’s quick to point out that dry eye is not something that can be resolved in a single visit. The ability of the eyes to maintain the appropriate amount of moisture depends on a delicate balance of Meibomian oil, adequate tears and proper blinking. Should these factors fall out of balance; the result can be inflammation which often cascades into problems resulting in even more discomfort.


“It is critical for the eye care practitioner to understand that a systematic approach is required to make the correct diagnosis before initiating treatment. While over 80 percent of all dry eye sufferers have meibomian obstruction and dysfunction, it is critical for the doctor to evaluate a minimum of four other factors; the nature of the blink, the efficacy of lid closure when sleeping, the extent of meibomian gland atrophy and the status of the sensory nerves,” Dr. Korb said. “One can treat with LipiFlow, but not achieve success for the patient unless all of these areas are addressed. The patient must understand that there will be homework, analogous to dental care, where office treatment must be supported by brushing and flossing.”


To colleagues and patients alike, Dr. Korb’s tireless work is fueled by a very rare level of passion and commitment. Whether he’s caring for patients or pursuing the next breakthrough in his research, Dr. Korb is a man on a mission. He is a deeply compassionate individual whose desire to learn about this affliction drives him to treat over 100 patients per month while still dedicating a minimum of three days per week to his research.'


When asked why he is so focused on this particular affliction and why he has made it his life’s mission, Dr. Korb is characteristically enthusiastic.


“Truthfully, some 35 years ago when I discovered the role of Meibomian gland dysfunction, I had plans to retire at an age which would allow me to follow my other interests, including working to help children pursue higher education in order to realize their own dreams. I also wanted to research the role of ego in mankind’s progress and failures – I still find this exciting.


“However, with every discovery, with every new publication, and with the creation of treatments, procedures and products for both patients and doctors, it was clear there was much more to accomplish. I still am excited every day by what I do and it is my hope that more can be accomplished to alleviate the suffering of over 30 million people in the USA with dry eye. Frankly, there is no area that provides me with the level of satisfaction and daily stimuli than what I do. I have been, and continue to be very fortunate.”


Korb and Associates is located at 400 Commonwealth Avenue in Boston. The office can be reached at 617-426-0370 or www.korbassociates.com.


http://www.fiftyplusadvocate.com/archives/11475

Mitotech eyes novel approach to treating Dry Eye Disease

Posted by australiandryeye on March 7, 2017 at 3:45 AM Comments comments (0)

An aging population, an ever increasing amount of time viewing digital devices and a growing trend in eye diseases are all factors expected to fuel a global increase in Dry Eye Disease. Currently, there are about 16 million people in the U.S. alone suffering from the condition, which is quickly becoming a common malady.

 

According to the research and consulting firm GlobalData, the global market for treating dry eye is expected to climb to an estimated $4.6 billion by 2024, more than doubling the estimated $2.2 billion market size of 2014.

 

Additionally, Dry Eye Disease has become associated with other conditions like glaucoma, rheumatoid arthritis, Sjogren's syndrome, post-LASIK surgery and patients taking anti-depressants, Dr. Penny Asbell, an ophthalmologist at the Mount Sinai Department of Ophthalmology in New York, said.

 

The condition causes a reduction of tears being produced needed to lubricate and nourish the front of the eye called the tear film. In a normal state, the layer provides the cornea and conjunctiva a healthy barrier from exposure as well as smoothing the anterior surface to provide the best optics for good vision. If the tear film becomes unhealthy and begins to break down symptoms of irritation as well as unstable and intermittently changing vision can happen.

 

Tear production tends to slow as people get older. By the time someone reaches 65 they can lose up to 65% of their tear volume compared to when they were 18. The condition can be exacerbated by medical conditions that begin to present themselves with age as well, by environmental influences like air pollution and windy, dry climates and by use of systemic medications.

 

Yet, it is not exclusive to seniors. Dr. Asbell said more cases are being reported in the young, most likely due to the increasing amount of time they spend looking at computer screens and digital devices that decreases the amount of blinking and lubrication of their eyes suffers.

 

Tears have a fairly intricate composition as they are made up of hundreds of different types of molecules, including natural antibiotics called lysozymes, vitamins, minerals, mucus, oil and water.

 

Dry Eye Disease is a persistent condition, much like chronic pain, that can interfere with quality of life due to constant dry, itchy, gritty feeling and red or swollen eyes. It is seen as a condition that is a multifactorial disease affected by inflammation, tissue degeneration and tear production deficit. It’s also one of the main reasons patients go to see an eye doctor.

 

Currently, there are only two FDA-approved treatments for Dry Eye Disease — Allergan’s Restasis and Shire’s Xiidra, which focus almost exclusively on suppressing inflammatory aspects of the disease.

 

Luxembourg-based Mitotech, which is a clinical stage biotechnology company focused on developing treatments for age-related disorders like Dry Eye Disease, recently received several U.S. patents covering various formulations of its lead compound SkQ1 and its use in ophthalmology.

 

“The interesting thing is that it’s a whole different mechanism improving cellular activity,” Dr. Asbell, who has had first-hand laboratory experience with SkQ1, said. “It’s totally different from Restasis and Xiidra. Both work as anti-inflammatory agents, but SkQ1 improves cellular function and has anti-oxidant effect.”

 

SkQ1 works on a cellular level by reducing damage caused by excessive reactive oxygen species (ROS), which are types of free radicals that play an important role in cell signaling. SkQ1 also selectively protects membrane’s cardiolipin from oxidation and by doing so prevents mitochondrial dysfunction and process of cell death called apoptosis. Another feature of the compound is that its oxidation chemistry allows it to be recycled in the mitochondria, creating a renewable antioxidant. The company has built its clinical development program to leverage SkQ1 across age-related disorders that could include treating neurodegenerative diseases like Parkinson’s and Alzheimer’s.

 

“SkQ1 was developed as an agent fighting a spectrum of age-related diseases at their root, which in our hypothesis is oxidative stress inside mitochondria,” Natalia Perekhvatova, Mitotech’s chief executive, said. “In case of Dry Eye Disease our ophthalmic solution Visomitin has been shown not only to suppress inflammation, but also to protect corneal and conjunctival cells from damage and to promote health of lacrimal glands, therefore addressing the disease from multiple angles.”

 

Mitotech’s program for the treatment of Dry Eye Disease is focused on Visomitin, which is approved in Russia and had a successful Phase II study in the U.S. that indicated statistically significant effect of SkQ1 on both signs and symptoms of dry eye.

 

The company is currently preparing Visomitin for Phase III trials, with a goal of getting the compound before the FDA by 2019.

 

“SkQ1’s innovation is that it is not a ‘me too’ drug,” Dr. Asbell said. “It’s a totally different way of addressing the problem of dry eye.”

http://www.fiercebiotech.com/sponsored/mitotech-eyes-novel-approach-to-treating-dry-eye-disease

When will the Flood Gates open?

Posted by australiandryeye on March 4, 2017 at 1:35 AM Comments comments (0)

 

Dry Eye Drug Development: When Will the Floodgates Open?

New therapies have the potential to turn the prescription market from a trickle to a deluge.

 

By René Luthe, Senior Associate Editor

 

Clinicians waiting for a new prescription drug for their long-suffering dry eye patients are going to have to wait a little longer. While many drug makers are on the case, their offerings will not be an option in the near future. Allergan's Restasis remains the only game in town in the way of prescription remedies. "The regulatory approval process for dry eye drugs is a nightmare," concedes EyeGate Pharma's president and chief executive officer, Stephen From.

 

What gives? Miami's William B. Trattler, MD, allows that part of the problem may be the FDA setting the bar too high. Yet the main problem, he believes, is dry eye's own peculiar nature. "Dry eye can be caused by aqueous deficiency or it can be due to poor tear film quality related to Meibomian gland dysfunction," Dr. Trattler notes. "Or, it can be a combination of these two forms of dry eye. Importantly, inflammation is present in both conditions."

 

However, not all the news is discouraging: Some drugs are inching closer to approval and researchers continue to gain valuable insights into the disease. Here's a snapshot of prescription dry eye remedies on the horizon.

 

More Obstacles Than Most

 

The combination of factors at work in dry eye disease is widely held to be the main reason for the lack of progress on the new-drug front. "The disease itself is highly variable," says Simon Chandler, PhD, director of clinical research at Ista Pharmaceuticals.

 

Eddy Anglade, MD, chief medical officer at Lux Biosciences, agrees. "There isn't a very good correlation between signs and symptoms," he says, "so trying to find that group of patients who have disease that will respond in a way that is convincing from a regulatory standpoint is challenging, given that the current regulatory approval standard is to demonstrate significance in a sign and in a symptom."

 

It has been so difficult to achieve, Mr. From points out, that no company has succeeded in getting a New Drug Application (NDA) filing approved. Where many drugs run aground, he says, is in trying to transition from phase 2 clinical trials to phase 3. "Most people worry about translating from animal models into humans," Mr. From explains. "In dry eye, we worry about phase 2 data translating into phase 3 — can somebody repeat a study a second time?"

 

Other experts familiar with FDA clinical trials and dry eye disease concur. Dry eye's variability means that when it is time for sponsors to scale their phase 2 trials to phase 3, the drug's efficacy may be harder to demonstrate. The disease's multifactorial nature also contributes to the difficulty in navigating the approval process. For each different cause, there is at least one way to potentially treat it. Matching the drug to the right kind of patient is crucial (see "Clinical Trial Pearls," below).

 

Part of the problem might reside with the regulatory process itself. The process for clearance of a new drug is complex and as the knowledge base concerning dry eye disease expands, the scientific basis for drug testing changes. According to Michael A. Lemp, MD, clinical professor at Georgetown and George Washington universities, "it was anticipated that the FDA would issue new guidelines for clinical trials in dry eye disease several years ago, but these have not been made public. The delay may rest with senior management within the Agency."

 

The result is that there is no "one-stop shopping" source where would-be sponsors can learn the guidelines for clinical trial endpoints. Instead, sponsors must go to the FDA and make a proposal as to how they would perform a clinical trial; the FDA reviews the proposal and informs the sponsor if it is acceptable, or which portions are acceptable or unacceptable.

 

"While the FDA is quite open to these inquires and willing to listen to novel ap proaches, many times companies new to this field feel as if they are guessing what the FDA wants," Dr. Lemp explains. "They wonder if the FDA has changed what is acceptable since the last time they heard. It's like trying to read the tea leaves."

 

Chugging Along

 

Despite the regulatory hurdles, some dry eye drugs are making slow but steady progress toward beleaguered physicians and their patients. Most are anti-inflammatories, so their approval would fulfill a wish of Dr. Trattler's. "I use pulses of topical steroids frequently for dry eye patients, and if there were additional anti-inflammatory drugs that could work in this area, that would be very helpful for patients, since dry eye is an inflammatory condition."

 

• EGP-437. The closest drug to the goal is EyeGate's EGP-437. Currently in a phase 3 efficacy study, it's a dexamethasonederived corticosteroid solution delivered to the eye via an iontophoretic drug delivery system that enables the drug to overcome the problem of low bioavailability that limits other topical agents. "You have to try to bypass natural barriers that are in place: the tear film and cornea," Mr. From says. "It's very difficult to get a large quantity of drug into the front of the eye, or any drug to the posterior pole of the eye for retinal diseases." Iontophoresis also allows EGP-437 to bypass the method physicians have had to resort to deliver large quantities of drug into the eye: needles.

 

The doughnut-shaped applicator holds a sponge saturated with drug; the applicator is placed on the sclera after a topical anesthetic is applied to prevent the patient's blinking. An electrode at the base of the applicator is connected to a small, handheld generator that supplies a charge. A negatively charged drug in the foam portion gets a negative charge to the electrode, thus using the principle of electrorepulsion to push the drug at a high velocity into the eye.

 

The process, Mr. From says, requires only a couple of minutes. "Depending on how high the current is, or how long we leave this on the eye, will dictate how much drug goes into the eye and how deep it penetrates into the eye."

 

EGP-437 is a small molecule. In its recently-completed phase 2 study, it was able to treat multiple signs and symptoms of dry eye, rather than just one in each category, Mr. From says, "So we actually had the lucky advantage of being able to choose the best sign and the best symptom for our phase 3 trial." Even better, he says, was its onset of action, which begins within hours. "If you're a Sjögren's patient and you have severe dry eye, you are in a lot of discomfort and pain" and at risk for scarring, Mr. From explains. Such patients would welcome a therapy with rapid onset of action. "No other drug that I'm aware of works as quickly as our drug is working," he says.

 

Although data from EyeGate's 83-patient phase 2 trial are not yet available, the company did say that staining decreased in both fluorescein and lissamine green dyes, that conjunctival redness was reduced and that tear film breakup time increased.

 

As for dosage, the drug would be administered in a physician's office, probably on a quarterly basis, according to Mr. From, depending on severity. The company has begun enrolling patients for the phase 3 clinical trial of approximately 180 planned. Mr. From anticipates that the trial should be completed during the first quarter of 2011, with top-line data available at the end of that period.

 

He describes EyeGate's approach as acute therapy for a chronic problem. "We are able to put so much drug in so quickly to the tissues of the eye that we're knocking down the inflammatory cascade very rapidly. The drug doesn't stay in the eye very long, but the pharmacological effect lasts for a long time."

 

• CF101. Can-Fite BioPharma Ltd. recently opened an Investigational New Drug application (IND) with the FDA for a phase 3 study of its lead drug, CF101, for treatment of moderate to severe dry eye disease. Dr. Pnina Fishman, Can-Fite's CEO, says that CF101 exerts an anti-inflammatory effect and also an immunomodulatory one. The study will be initiated in few months.

 

An earlier phase 2 study, in which CF101 was taken orally as a monotherapy for 12 weeks, showed a statistically significant benefit in the clearing of fluorescein staining in the nasal, temporal, pupillary and inferior cornea, the company reports. CF101 also was found to be safe and well tolerated in the Phase 2. Further, the study showed a decrease in intraocular pressure in patients with dry eye, findings that have prompted Can-Fite to initiate a phase 2 clinical study for the drug's treatment of glaucoma.

 

The randomized, double-masked phase 3 trial will compare two oral doses of CF101 to placebo. Approximately 240 patients will be enrolled at multiple centers, to be treated for 24 weeks. The clinical endpoints are improvement of corneal fluorescein staining, tear production and dry eye symptom score.

 

• Low-dose bromfenac. Ista Pharmaceuticals' phase 2 trial of low-dose bromfenac (Remura) demonstrated improvement in both a key sign (lissamine green staining) and in symptoms (as measured by the Ocular Surface Disease Index) of dry eye in 38 patients over a six-week period. Further, patients treated with low-dose bromfenac maintained the improvement in signs and symptoms for 10 days after discontinuing treatment. The company is currently in the process of initiating the efficacy portion of the phase 3 program, which will entail two studies with a total of approximately 1,000 patients followed over a six-week period, according to Dr. Chandler. The safety portion of the phase 3 trial is tentatively scheduled to begin later this year and will comprise a six-month and a 12-month trial, with a total of approximately 4,000 patients.

 

Dr. Chandler notes that low-dose bromfenac could address the impact of inflammation on the ocular surface, a central feature of dry eye. "Controlling inflammation could both quiet the symptoms — that is, irritation, dryness, gritty, sandy feeling, burning in some cases — and improve the signs, such as staining, of ocular surface disease," he explains. The approach yields a dual benefit, Dr. Chandler contends, because of bromfenac's efficacy in dealing with pain as well as its ability to interrupt the inflammatory cycle, thereby allowing the ocular surface to heal. "There are very few medications that truly address the inflammatory cascade that is central to the disease while improving patient comfort," he says.

 

Although the inflammatory etiology of dry eye remains theoretical, Dr. Chandler says it does explain the results seen in the phase 2 open-label trial. Dr. Chandler contends that low-dose bromfenac has an onset of action that is "much faster" than the approximately eight weeks required for topical cyclosporine. In studies completed to date, he says, the drug produced a response rate that hovers around 70%.

 

Regarding safety, Dr. Chandler points out that higher-dose bromfenac studied in more than 1,600 patients did not result in any serious corneal adverse events; ocular adverse events observed in these studies resolved with no sequelae. From the perspective of global clinical experience with bromfenac, in about 19 million ophthalmic uses of the currently marketed higher concentration, there have been 22 serious corneal adverse events reported overall. Not all were considered drug related, Dr. Chandler points out, and most were in subjects who had undergone cataract surgery. "Lowering the concentration of bromfenac as we have done could further reduce the likelihood of severe corneal adverse events," he says. As part of its commitment to patient safety, Ista has incorporated frequent monitoring of the cornea into the protocols for the large safety trials being planned.

 

• SAR 1118. Sarcode Corp. says that the phase 2 results for SAR-118, a topical small-molecule lymphocyte function-associated antigen-1 antagonist, showed clear improvements in signs and symptoms of dry eye at 12 weeks. The trial was a randomized, multisite, doublemasked study involving 230 subjects. Various dose levels (0.1, 1.0 and 5.0%) were compared to placebo, with subjects receiving the drops BID for 12 weeks. The primary objective measure was inferior corneal staining; major secondary measures were OSDI symptom score and tear production by Schirmer test. The company will present full details of the phase 2 study in spring 2011. Sarcode is currently preparing for a phase 3 trial to begin in mid-2011.

 

• Mapracorat. Bausch + Lomb is addressing the issue of tear hyperosmolarity in dry eye disease, which research suggests is a mechanism involved in ocular surface inflammation, with its selective glucocorticoid receptor agonist (mapracorat), currently in phase 2 trials. In vitro studies suggest mapracorat inhibits hyperosmolar-induced cytokine release and mitogenactivated protein kinase pathways in human corneal epithelial cells. Development of the compound continues to progress as a novel product with a new mechanism of action for the treatment of dry eye, according to B+L.

 

A study in the September 2010 issue of Molecular Vision showed it to have comparable activity to dexamethasone in combating inflammation. The investigators evaluated mapracorat's anti-inflammatory effects in an in vitro osmotic stress model that induced hyperosmolar conditions in cultured human corneal cells. The model stimulated the release of pro-inflammatory cytokines interleukin-6, interleukin-8 and monocyte chemotactic protein-1, and also altered the phosphorylation state of p38 and c-Jun N-terminal kinase (JNK), and the transcriptional activity of NFkappaB and AP-1. The researchers found that the incubation of cells with mapracorat inhibited hyperosmolarinduced cytokine release with potency comparable to the dexamethasone control group. Additionally, increased phosphorylation of p38 and JNK caused by hyperosmolarity was inhibited by mapracorat, and the compound caused a significant decrease in the hyperosmolar-induced rise in NFkappaB and AP-1 transcriptional activity.

 

• RX-10045. One of a class of medicines called resolvins, RX-10045 is a small-molecule lipid mediator that Resolvyx Pharmaceuticals says activates the body's own mechanisms for shutting off inflammation. It is administered as a topical eye drop. Resolvyx completed a phase 2 trial last year for chronic dry eye. In the randomized, placebo-controlled, 232-patient trial, RX-10045 produced dose-dependent, statistically significant improvement on the primary endpoints for both the signs and symptoms of dry eye, and was generally shown to be safe and well tolerated, the company says.

 

The phase 2 study examined three doses of RX-10045 and used a controlled adverse environment (CAE) simulator to measure corneal staining in a stressful drying environment, as well as daily patient diaries using a standard visual analog scale to assess symptom improvement over the course of the 28-day study. The drug produced a significant dosedependent improvement from baseline in symptoms recorded in daily patient diaries. It also reduced staining of the central cornea by 75% (P<0.00001) versus placebo, the difference approaching statistical significance (P=0.11). Additionally, the drug showed a significant improvement in CAE-induced staining in the inferior cornea and in the composite of central and inferior cornea, which also approached statistical significance over placebo (P=0.09).

 

Resolvyx says the phase 3 trial should begin by the end of the year.

 

• AzaSite. Currently there is no prescription product indicated for blepharitis, a void Inspire Pharmaceuticals would like to fill with AzaSite (azithromycin). The drug is already approved as a treatment for bacterial conjunctivitis, but it did not meet statistically significant endpoints in two phase 2 trials for anterior blepharitis last spring. Though a four-week trial did demonstrate improvement in measured signs and symptoms compared to placebo, statistical significance was not achieved for the primary endpoint of mean lid margin hyperemia.

 

On the secondary endpoints, however, Inspire president and chief executive officer Adrian Adams reports seeing some statistical significance in the areas of signs and symptoms. In the two-week trial, there were no statistically significant improvements for AzaSite compared to vehicle; this included the primary endpoint of clearing of lid debris.

 

The company says it will use the data obtained from these studies to continue to develop trial parameters using AzaSite as a treatment for both anterior and posterior blepharitis, and expects to refine the trial design through the end of this year. The refinement will include study populations and "seeking improved mappability for assessing and measuring signs and symptoms," says Mr. Adams. "With that, we are looking to utilize the photographic reading centers to maximize the trial."

 

Inspire anticipates completing the additional phase 2 AzaSite clinical work in 2011. The initiation of the phase 3 trial should begin sometime later next year.

 

• LX-214. Lux Biosciences' dose-ascending phase 1 trial showed that LX-214, a novel topical formulation of voclosporin, was well tolerated by healthy volunteers. There was no difference in tolerability between the vehicle control and the concentrations of drug tested (0.2% and 0.02%). In five subjects diagnosed with dry eye syndrome, the cohort "showed some improvement in their signs (measured by Schirmer's tear test) and symptoms (measured by the OSDI); most notably, the changes observed occurred in the relatively brief timeframe of the study, two weeks compared to what has been reported previously with cyclosporine emulsion," according to Dr. Anglade.

 

Voclosporin affects the immune response at the surface of the eye, he explains. "We think by controlling the local inflam matory response, it will allow the tear-producing lacrimal gland and the surface of the eye to heal and improve tear production.

 

LX-214 belongs to a class of agents known as calcineurin phosphatase inhibitors, developed by the company into a nanomicellar formulation. "This renders LX214, a highly insoluble compound, a solution as opposed to an emulsion," Dr. Anglade explains. He believes the drug's solution formulation will help make it better tolerated than cyclosporine emulsion.

 

Another advantage, says Dr. Anglade, is voclosporin's higher concentration. "A limitation of other forms of topical cyclosporine is that sufficiently high concentrations may not be achieved locally. The ability to achieve high local concentrations may translate into improved efficacy. We'll be able to assess that concept hopefully in the phase 3 when we do a large dose-ranging study."

 

Dr. Anglade adds that the company is planning a phase 2 proof-of-concept study for the near future.

 

• Restasis X. Allergan reports that it is currently testing a new variation of cyclosporine, Restasis X, in phase 2 clinical trials. The company is not able to speculate on expected timing for FDA approval.

 

In related news, in a study published in the August issue of the British Journal of Ophthalmology, researchers evaluated the efficacy and safety of two concentrations (0.05% and 0.1%) of cyclosporine A in aqueous solution compared to vehicle in treating the signs and symptoms of moderate-tosevere dry eye patients.1 At Day 21, the 1% group showed statistically significant improvement (p<0.05) in four symptoms and three ocular signs; the 0.05% showed statistically significant improvement in three symptoms and three signs; and the vehicle-only group in two symptoms and two signs. According to the researchers, at Day 42, the 0.1% group performed demonstrated improvement in four symptoms, while the 0.05% group demonstrated improvement in one symptom and one sign.

 

Hope for The Future

 

Dr. Lemp's vantage point as a participant in many FDA trials gives him reason to believe that the regulatory situation for dry eye drugs will soon improve. "As we learn more about the pathological processes at work in dry eye disease, new treatment strategies are emerging and data to support new endpoints are being published," he notes.

 

For one thing, in a meeting earlier this year, the FDA's Wiley Chambers, MD, expanded the criteria for primary endpoints that the agency will accept, including studies that document a correlation between signs and symptoms. Included in that slide was a list of inflammatory cytokines in the tears and tear osmolarity. "That's new," says Dr. Lemp. "That's potentially big."

 

Patient-reported outcomes are gaining favor with the FDA as well. The most common vehicle for reporting patient symptoms has been the 100-point scale OSDI. However, showing the required 29-point improvement in symptoms has been onerous. It has required sponsors to find patients who were highly symptomatic — "Who at least start out with 50 to 60 points on the scale," Dr. Lemp says. "And that rules out 90% of the population with dry eye."

 

New studies re-examining the relationships between subjective patient changes and levels of disease severity, novel ways to assess patient-reported improvement and a better understanding of the relationship between signs and symptoms in dry eye disease all have the potential to open the door to less onerous but scientifically rigorous study designs, Dr. Lemp notes. He believes that this augurs well for demonstration of clinical efficacy and the appearance of an expanded therapeutic portfolio of drugs for the more effective management of dry eye disease.

 

Perhaps the best reason to believe that the fortunes of prescription dry eye drugs will improve? "Let's put it this way, to my knowledge, there are probably more than 30 drugs in the pipeline," says Dr. Lemp. Many companies are investing in the dry eye market, and not just "the usual suspects" such as Alcon, Allergan and B+L.

 

The fact that Restasis could generate an approximate half a billion dollars in revenue last year despite its demonstrated effect in only about 15% of the patients studied (according to the package label), indicates significant unmet medical need and a healthy bottom line for those willing to invest.

 

With industry on board and the FDA willing to update its clinical trial criteria, the conditions for victories seem to be increasingly in place. OM

 

Reference

 

1. Baiza-Durán L, Medrano-Palafox J, Hernández-Quintela E, Lozano-Alcazar J, Alaníz-de la O JF. A comparative clinical trial of the efficacy of two different aqueous solutions of cyclosporine for the treatment of moderate-to-severe dry eye syndrome. Br J Ophthalmol. 2010 Aug 1. [Epub ahead of print]

http://www.ophthalmologymanagement.com/issues/2010/november-2010/dry-eye-drug-development-when-will-the-floodgates


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